title: Effect of bisphenol A on pluripotency of mouse embryonic stem cells and differentiation capacity in mouse embryoid bodies.
abstract: Bisphenol A (BPA) poses potential risks to reproduction and development. However, the mechanism of BPA's effects on early embryonic development is still unknown. Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro models for testing the toxic effects of environmental chemicals in early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were exposed to BPA up to 6 days and their differentiation capacity was evaluated. In mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of endodermal markers (Gata4,Sox17) and mesodermal markers (Sma,Desmin), and reduced the mRNA levels of ectodermal markers (Nestin,Fgf5) in mEB. Furthermore, microRNA(miR)-134, an expression inhibitor of pluripotency markers including Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These results firstly indicate that BPA may disturb pluripotency in mESC and differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB while miR-134 may play a key role underlying this effect.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Xiumei
authors.initials: X
authors.lastname: Han
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Mao
authors.forename: Prue
authors.initials: P
authors.lastname: Talbot
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Guizhen
authors.initials: G
authors.lastname: Du
authors.forename: Aiqin
authors.initials: A
authors.lastname: Chen
authors.forename: Jiayin
authors.initials: J
authors.lastname: Liu
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D018398:Homeodomain Proteins; D035683:MicroRNAs; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D010636:Phenols; D055748:SOXB1 Transcription Factors; C551912:Mirn134 microRNA, mouse; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse; C527783:Sox2 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide; AP; BPA; Bisphenol A; Differentiation; MTT; MicroRNA; Mouse embryoid bodies; Mouse embryonic stem cells; Pluripotency; alkaline phosphatase; bisphenol A; mEB; mESC; mouse embryoid bodies; mouse embryonic stem cells